Richard J. Roller, Ph.D.
Ph.D., Harvard University, 1987 |
Professor and Vice Chairman of Microbiology Campus address: 3-432 BSB Mailing address: 51 Newton Rd. 3-432 Bowen Science Building Iowa City, IA 52242 Phone: 319-335-9958 Email: |
Molecular Biology of Herpes Simplex Infections
Herpesvirus genomes are transcribed and replicated in the nucleus of the cell. Virus capsids are assembled, and viral genomes are packaged into those capsids in the nucleus as well. The DNA containing capsids must then be transported to the cytoplasm. Capsids are enveloped by the inner nuclear membrane, forming a virus particle between the inner and outer nuclear membranes. The envelope of this virus particle then fuses with the outer nuclear membrane, releasing the DNA-containing capsid to the cytoplasm, where it can finish maturation and egress. This process of nuclear envelopment/de-envelopment is conserved in all herpesviruses and uses virus proteins that are not closely related to any cellular proteins. As such, it represents a very attractive target for development of new antiviral therapies for herpesviruses.
My lab is interested in the mechanism of nuclear envelopment. We have identified some of the viral factors required for the process and hope to create a complete description of the process by (i) identifying all of the viral and cellular factors required; (ii) assigning functions to each of those factors; (iii) characterizing all of the functional interactions tat are necessary for this process; (iv) determining the structures of critical parts of the envelopment apparatus (v) identifying points in the process that might be susceptible to inhibition.
Herpesvirus nuclear envelopment is associated with changes in the organization of the nuclear lamina – a complex structure that underlies the inner nuclear membrane and that plays critical roles in maintaining nuclear structure, in assembling and disassembling the nucleus during cell division, and in regulating gene expression. Our research has recently focused on the means by which the virus alters the structure of the lamina during infection. This research has implications not only for the biology of herpesviruses, but also for the understanding of nuclear function and of human diseases that result from changes in the structure of the nuclear lamina.
Virus-infected cells can be eliminated by apoptosis, a kind of programmed cell death. Apoptosis can be induced either by sensing mechanisms within the infectedc cell itself, or by cells of the immune system after they recognize an infected cell. Like many viruses, herpes simplex virus has evolved ways of inhibiting apoptosis in the infected cell. One critical anti-apoptotic factor for HSV is a virus-encoded protein kinase called US3 that is also involved in primary envelopment. We are intrigued by the overlap in functions in this protein and are working to determine the mechanisms by which it inhibits apoptosis and participates in envelopment.
Recent publications
Leach, N., S.L. Bjerke, D.K. Christensen, J.M. Bouchard, F. Mou, R. Park, J.D. Baines, T. Haraguchi, and R.J. Roller. 2007. Emerin is hyperphosphorylated and redistributed in herpes simplex virus type 1-infected cells in a manner dependent upon both UL34 and US3. J. Virol. 81:10792-10803.
Farnsworth, A., T.W. Wisner, M. Webb, R. Roller, G. Cohen, R. Eisenberg, and D.C. Johnson. 2007. Herpes simplex virus glycoproteis gB and gH function in fusion between the virion envelope and the outer nuclear membrane. Proc. Natl. Acad. Scie. USA 104:10187-10192.
Bjerke, S.L. and R.J. Roller. 2006. Roles for herpes simplex virus type 1 UL34 and US3 proteins in disrupting the nuclear lamina during herpes simplex virus type 1 egress. Virology 347:261-276.